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The receptor PD-1 controls follicular regulatory T cells in the lymph nodes and blood
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Journal Article
The receptor PD-1 controls follicular regulatory T cells in the lymph nodes and blood
2013
Overview
Follicular regulatory T cells control humoral immune responses, but how these cells are in turn controlled has been unclear. Sharpe and colleagues demonstrate that signaling via PD-1 regulates number and function of these cells.
CD4
+
CXCR5
+
Foxp3
+
follicular regulatory T cells (T
FR
cells) inhibit humoral immunity mediated by CD4
+
CXCR5
+
Foxp3
−
follicular helper T cells (T
FH
cells). Although the inhibitory receptor PD-1 is expressed by both cell types, its role in the differentiation of
T
FR
cells is unknown. Here we found that mice deficient in PD-1 and its ligand PD-L1 had a greater abundance of
T
FR
cells in the lymph nodes and that those
T
FR
cells had enhanced suppressive ability. We also found substantial populations of
T
FR
cells in mouse blood and demonstrated that
T
FR
cells in the blood homed to lymph nodes and potently inhibited T
FH
cells
in vivo
.
T
FR
cells in the blood required signaling via the costimulatory receptors CD28 and ICOS but were inhibited by PD-1 and PD-L1. Our findings demonstrate mechanisms by which the PD-1 pathway regulates antibody production and help reconcile inconsistencies surrounding the role of this pathway in humoral immunity.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ Animals
/ Blood
/ Cell Communication - immunology
/ Inducible T-Cell Co-Stimulator Protein - blood
/ Inducible T-Cell Co-Stimulator Protein - genetics
/ Inducible T-Cell Co-Stimulator Protein - immunology
/ Mice
/ Programmed Cell Death 1 Receptor - blood
/ Programmed Cell Death 1 Receptor - genetics
/ Programmed Cell Death 1 Receptor - immunology
/ Signal Transduction - immunology
/ T cells
/ T-Lymphocytes, Helper-Inducer - cytology
/ T-Lymphocytes, Helper-Inducer - immunology
